The long-term goal of this project is to contribute to a better understanding of the physiological, pharmacological, evironmental and developmental factors influencing or controlling pyrimidine synthesis in normal and neoplastic mammalian tissues. Emphasis will be placed on a study of the structure and activity of a bifunctional enzyme complex comprised of orotate phosphoribosyltransferase and orotidylate decarboxylase. Recent evidence has indicated that such a complex might be widely distributed in animals and humans. Although hybrid mice will serve as the primary source of these two enzymes, plans also call for an examination of these enzymes from other animals, murine neoplasms and humans.